Abstract：
Cutaneous squamous cell carcinoma (cSCC) ranks as the second most prevalent skin tumour (excluding melanoma). However, the molecular mechanisms driving cSCC progression remain elusive. This study aimed to investigate GBP1 expression in cSCC and elucidate its potential molecular mechanisms underlying cSCC development. GBP1 expression was assessed across public databases, cell lines and tissue samples. Various assays, including clone formation, CCK8 and EdU were employed to evaluate cell proliferation, while wound healing and transwell assays determined cell migration and invasion. Subcutaneous tumour assays were conducted to assess in vivo tumour proliferation, and molecular mechanisms were explored through western blotting, immunofluorescence and immunoprecipitation. Results identified GBP1 as an oncogene in cSCC, with elevated expression in both tumour tissues and cells, strongly correlating with tumour stage and grade. In vitro and in vivo investigations revealed that increased GBP1 expression significantly enhanced cSCC cell proliferation, migration and invasion. Mechanistically, GBP1 interaction with SP1 promoted STAT3 activation, contributing to malignant behaviours. In conclusion, the study highlights the crucial role of the GBP1/SP1/STAT3 signalling axis in regulating tumour progression in cSCC. These findings provide valuable insights into the molecular mechanisms of cSCC development and offer potential therapeutic targets for interventions against cSCC.
摘要：
皮肤鳞状细胞癌（cSCC）是第二常见的皮肤肿瘤（不包括黑色素瘤）。然而,驱动cSCC进展的分子机制仍然难以捉摸。本研究旨在研究GBP1在cSCC中的表达，并阐明其潜在的cSCC发生发展的分子机制。GBP1表达在公共数据库中进行评估，细胞系和组织样本。各种化验，包括克隆形成，CCK8和EdU用于评估细胞增殖，而伤口愈合和transwell测定确定细胞迁移和侵袭。进行皮下肿瘤测定以评估体内肿瘤增殖，通过蛋白质印迹研究了分子机制，免疫荧光和免疫沉淀。结果确定GBP1是cSCC的癌基因，在肿瘤组织和细胞中表达升高，与肿瘤分期和分级密切相关。体外和体内研究表明，增加的GBP1表达显着增强cSCC细胞增殖，移民和入侵。机械上,GBP1与SP1的相互作用促进了STAT3的激活，导致恶性行为。总之,该研究强调了GBP1/SP1/STAT3信号轴在调节cSCC肿瘤进展中的关键作用.这些发现为cSCC发展的分子机制提供了有价值的见解，并为针对cSCC的干预措施提供了潜在的治疗靶标。
